Clinical outcomes of progressive supranuclear palsy and multiple system atrophy

Abstract

Prognostic predictors have not been defined for progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Subtypes of both disorders have been proposed on the basis of early clinical features. We performed a retrospective chart review to investigate the natural history of pathologically confirmed cases of PSP and MSA. Survival data and several clinically relevant milestones, namely: frequent falling, cognitive disability, unintelligible speech, severe dysphagia, dependence on wheelchair for mobility, the use of urinary catheters and placement in residential care were determined. On the basis of early symptoms, we subdivided cases with PSP into 'Richardson's syndrome' (RS) and 'PSP-parkinsonism' (PSP-P). Cases of MSA were subdivided according to the presence or absence of early autonomic failure. Sixty-nine (62.7%) of the 110 PSP cases were classified as RS and 29 (26.4%) as PSP-P. Of the 83 cases of MSA, 42 (53.2%) had autonomic failure within 2 years of disease onset. Patients with PSP had an older age of onset (P < 0.001), but similar disease duration to those with MSA. Patients with PSP reached their first clinical milestone earlier than patients with MSA (P < 0.001). Regular falls (P < 0.001), unintelligible speech (P = 0.04) and cognitive impairment (P = 0.03) also occurred earlier in PSP than in MSA. In PSP an RS phenotype, male gender, older age of onset and a short interval from disease onset to reaching the first clinical milestone were all independent predictors of shorter disease duration to death. Patients with RS also reached clinical milestones after a shorter interval from disease onset, compared to patients with PSP-P. In MSA early autonomic failure, female gender, older age of onset, a short interval from disease onset to reaching the first clinical milestone and not being admitted to residential care were independent factors predicting shorter disease duration until death. The time to the first clinical milestone is a useful prognostic predictor for survival. We confirm that RS had a less favourable course than PSP-P, and that early autonomic failure in MSA is associated with shorter survival.

Epidemiology of Multiple System Atrophy in Hokkaido, the Northernmost Island of Japan

“…In our study, this association was confirmed by differences found in the survival analysis based on onset symptoms. Other studies have reported that patients with autonomic failure at disease onset had worse prognoses than those that exhibited cerebellar ataxia at onset [19,20]. In the current study, we found the same association even though the definition of autonomic failure in the national registry might be different from that in previous studies.…”

Network correlates of disease severity in multiple system atrophy

“…18 By contrast, functional disability is closely associated with the severity of motor symptoms, 16 and standardized rating scales are currently being used to measure disease progression in MSA experimental trials. 19 -21 Given the variability inherent in such clinical descriptors, alternative quantifiers of disease severity/progression may enhance the accuracy and speed of experimental trials of new MSA therapies.…”

Parkinsonian Syndromes

“…31 Motor and autonomic features lead to major disability. Early autonomic failure; older age of onset; short interval from disease onset to frequent falling, cognitive disability, unintelligible speech, severe dysphagia, dependence on wheelchair for mobility, and urinary catheter use; and lack of admission to a nursing home facility independently predict short disease survival.…”

“…The mean disease duration from onset to death is about 7 years. 31 Progressive supranuclear palsyparkinsonism. In contrast to patients with PSP-Richardson syndrome, PSPparkinsonism patients develop bradykinesia and limb rigidity at disease onset, which can be asymmetric and, in some cases, associated with a jerky action or rest tremor.…”